US 2004O147605A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0147605 A1 Onuki et al. (43) Pub. Date: Jul. 29, 2004

(54) DRUG PREPARATIONS (86) PCT No.: PCT/P02/05041 (76) Inventors: Yoichi Onuki, Chiba (JP); Minoru (30) Foreign Application Priority Data Okada, Chiba (JP); Hirotaka Sakai, Chiba (JP); Hideyoshi Kanbe, Chiba May 25, 2001 (JP)...... 2001-156853 (JP); Hiroyuki Mizuno, Chiba (JP); Katsumi Imamori, Chiba (JP) Publication Classification Correspondence Address: (51) Int. Cl." ...... A61K 31/198 OBLON, SPIVAK, MCCLELLAND, MAIER & (52) U.S. Cl...... 514/561 NEUSTADT, P.C. 1940 DUKE STREET (57) ABSTRACT ALEXANDRIA, VA 22314 (US) Drug preparations characterized by containing fudosteine (21) Appl. No.: 10/477,755 and an antituSSive. These preparations are drugs to be used for common cold, etc. which have improved antituSSive and (22) PCT Filed: May 24, 2002 Sputum-removal effects. US 2004/O147605 A1 Jul. 29, 2004

DRUG PREPARATIONS 0011 Although there are no specific limitations to the amount of fudosteine or its Salt in the drug composition of TECHNICAL FIELD the present invention, a dose for an adult is usually about 0001. The present invention relates to a drug preparation, 12-2,400 mg/day, and more preferably about 40-1,200 more particularly, to a drug preparation that has antituSSive mg/day. and expectorant effects and can be advantageously used as 0012 Examples of the antitussive used in the drug prepa an antituSSive expectorant or the like. ration of the present invention include alloclamide hydro chloride, cloperastine hydrochloride, pentoxyverine citrate, BACKGROUND ART tipepidine citrate, Sodium dibunate, dextromethorphan 0002 Conventionally, an antitussive component and hydrobromide, dextromethorphan phenolphthalin Salt, tipe expectorant component are added to many drug preparations pidine hibenzate, cloperastine fendizoate, codeine phos for colds, Since diseases Such as the common cold cause phate, dihydrocodeine phosphate, trimetoquinol hydrochlo coughs and Sputum. Many antituSSive expectorants that ride, phenylpropanolamine hydrochloride, mainly aim to Suppress coughs and remove Sputum are also methoxyphenamine hydrochloride, dl-methylephedrine commercially available. hydrochloride, 1-methylephedrine hydrochloride, noScapine hydrochloride, noScapine, ephedra herb, nandina fruit, dil 0003. However, the commercially available drug prepa methylephedrine Saccharin Salt, carbetapentane citrate, rations for colds are not Sufficiently effective in Suppressing dimenorfan phosphate, beinproperine phosphate, isoaminile coughs and removing Sputum, Since the amount of the citrate, OXeladin citrate, OXeladin tannate, eprazinone hydro antituSSive and expectorant components is limited. Neither chloride, clobutinol hydrochloride, clo?edanol hydrochlo are the commercially available antituSSive expectorants Suf ride, fominoben hydrochloride, cloperastine hydrochloride, ficiently effective, particularly in the antituSSive effect. oxymethebanol, opium, ethylmorphine hydrochloride, mor 0004. Therefore, development of drug preparations hav phine hydrochloride, morphine Sulfate, opium alkaloids ing an improved antituSSive effect has been desired. hydrochlorides, TRK-851, and CS-003. These can be used either individually or in combination of two or more. DISCLOSURE OF THE INVENTION 0013 The amount of the antitussive in the drug prepa 0005. In order to obtain drug preparations having ration of the present invention is determined based on the improved antituSSive and expectorant effects, the present type and amount of other medicines used in combination inventors have Studied the efficacy of various antituSSives according to a known formulation technique. A dose for an and their combinations with other medicinal components adult is usually 1 mg to 20 g/day, and preferably 1.2 mg to and have found that if fudosteine, which is useful as an 10 g/day. expectorant but does not exhibit an antituSSive effect by 0014 Besides the above essential medicinal components, itself, is combined with an antituSSive, the antituSSive can other medicinal components may be added to the drug exhibit a markedly enhanced antitussive effect. This finding preparation of the present invention. For example, one or has led to the completion of the present invention. more medicinal components Selected from the group con 0006 Specifically, the present invention provides drug Sisting of a bronchodilator, antihistamine, analeptic, galeni preparations containing fudosteine and an antituSSive. cal, antacid or mucosal protective agent, and bactericide may be added. BEST MODE FOR CARRYING OUT THE 0015 Examples of the bronchodilator include amino INVENTION phylline, diprophylline, theophylline, proxyphylline, cho 0007 Fudosteine and an antitussive are added to the drug line theophylline, epinephrine, ephedrine hydrochloride, preparation of the present invention as essential medicinal isoprenaline Sulfate, isoprenaline hydrochloride, orciprena components. line Sulfate, clorprenaline hydrochloride, Salbutamol Sulfate, terbutaline sulfate, tulobuterol hydrochloride, procaterol 0008. The fudosteine used in the present invention is hydrochloride, fenoterol hydrobromide, formoterol fuma S-(3-hydroxypropyl)-L-cysteine of the following formula (I) rate, clenbuterol hydrochloride, mabuterol hydrochloride, that has been already reported to be useful as an expectorant ipratropium bromide, flutropium bromide, OXitropium bro in Japanese Patent Application Laid-open No. 2-3674. mide, tiotropium bromide, Salmeterol Xinafoate, hexoprena line sulfate, Ro 25-1553, and a vasoactive intestinal peptide/ (I) pituitary adenylate cyclase activating polypeptide derivative HO-(CH2)4-S-CH2-CH-COOH (VIP/PACAP derivative). These can be used either individu ally or in combination of two or more. 0016. The amount of the bronchodilator is determined based on the type and amount of other medicines used in 0009. However, a drug preparation to which the combination according to a known formulation technique. A fudosteine and an antituSSive are added has not yet been dose for an adult is usually 10 ug to 1,000 mg/day, and known. preferably 42-600 mg/day. 0010. In the drug composition of the present invention, 0017 Examples of the antihistamine include isothipendyl fudosteine or its Salt Such as an inorganic acid Salt, organic hydrochloride, iproheptine hydrochloride, difeterol hydro acid Salt, alkaline metal Salt, or alkaline earth metal Salt of chloride, diphenylpyraline hydrochloride, diphenhydramine fudosteine can be used. hydrochloride, triprolidine hydrochloride, tripelennamine US 2004/O147605 A1 Jul. 29, 2004 hydrochloride, thonzylamine hydrochloride, fenethazine gel, aluminum hydroxide-magnesium carbonate mixture co hydrochloride, promethazine hydrochloride, diphenhy dried gel, aluminum hydroxide-Sodium hydrogencarbonate dramine Salicylate, carbinoxamine diphenyldisulfonate, coprecipitate, aluminum hydroxide-calcium carbonate-mag alimemazine tartrate, diphenhydramine tannate, diphe nesium carbonate coprecipitate, magnesium hydroxide-alu nylpyraline theoclate, promethazine methylene disalicylate, minum potassium Sulfate coprecipitate, magnesium alumi carbinoxamine maleate, d1-chlorpheniramine maleate, nometasilicate, magnesium hydroxide, aluminum Sulfate, d-chlorpheniramine maleate, difeterol phosphate, methdila and sucralfate. These can be used either individually or in Zine hydrochloride, mebhydroline napadisylate, meduita combination of two or more. Zine, cyproheptadine hydrochloride, clemastine fumarate, epinastine hydrochloride, olopatadine hydrochloride, feX 0024. The amount of the antacid or mucosal protective agent is determined based on the type and amount of other ofenadine hydrochloride, loratadine, bepotastine besilate, medicines used in combination according to a known for mizolastine, and NIP-531. These can be used either indi mulation technique. A dose for an adult is usually 10-8,000 vidually or in combination of two or more. mg/day, and preferably 100-4,000 mg/day. 0.018. The amount of the antihistamine is determined 0025 Examples of the bactericide include cetylpyridium based on the type and amount of other medicines used in combination according to a known formulation technique. A chloride, dequalinium chloride, and chlorhexidine hydro dose for an adult is usually 1-300 mg/day, and preferably chloride. These can be used either individually or in com 3-150 mg/day. bination of two or more. 0026. The amount of the bactericide is determined based 0.019 Examples of the analeptic include caffeine and on the type and amount of other medicines used in combi Sodium benzoate, caffeine, anhydrous caffeine, dl-methyl nation according to a known formulation technique. A dose ephedrine hydrochloride, dl-methylephedrine Saccharin Salt, for an adult is usually 0.05-50 mg/day, and preferably ephedrine hydrochloride, phenylpropanolamine hydrochlo 0.125-5 mg/day. ride, phenylephrine, l-methylephedrine hydrochloride, methoxyphenamine hydrochloride, d1-epinephrine hydro 0027) A vitamin and antiinflammatory enzyme maybe chloride, dl-isoproterenol hydrochloride, isoproterenol Sul further added to the present drug preparation. fate, orciprenaline Sulfate, terbutaline Sulfate, Salbutamol 0028. Examples of the vitamin include vitamin B1 and its Sulfate, trimethoduinol hydrochloride, heXoprenaline Sul derivatives Such as Octotiamine, proSultiamine, furSul fate, clorprenaline hydrochloride, tulobuterol hydrochloride, tiamine, furSultiamine hydrochloride, bisbentiamine, benfo procaterol hydrochloride, pirbuterol hydrochloride, fenot tiamine, dicethiamine hydrochloride, cycotiamine, cocar erol hydrobromide, formoterol fumarate, clenbuterol hydro boxylase, thiamine disulfide, thiamine hydrochloride, chloride, mabuterol hydrochloride, ethylcysteine hydrochlo thiamine nitrate, bisthiamine nitrate, thiamine dicetylsulfate, ride, methylcysteine hydrochloride, and pseudoephedrine. and bisibutiamine, salts thereof, vitamin B2 and its deriva These can be used either individually or in combination of tives such as riboflavin, riboflavin butyrate, riboflavin tWO Or more. Sodium phosphate, and flavin adenine dinucleotide Sodium, 0020. The amount of the analeptic is determined based on Salts thereof, Vitamin C and its derivatives Such as ascorbic the type and amount of other medicines used in combination acid, Sodium ascorbate, and calcium ascorbate, Salts thereof, according to a known formulation technique. A dose for an hesperidin and its derivatives, Salts thereof, Vitamin F, adult is usually 1-900 mg/day, and preferably 5-300 mg/day. Vitamin A and its derivatives Such as retinol acetate and retinol palmitate, Salts thereof, Vitamin E and its derivatives 0021 Examples of the galenical include powders of Such as tocopherol Succinate, tocopherol calcium Succinate, galenicals. Such as ephedra herb, nandina fruit, Japanese tocopherol acetate, and tocopherol, and Salts thereof. These cherry bark, polygala root, glycyrrhiza, platycodon root, can be used either individually or in combination of two or apricot kernel, plantago Seed, plantago herb, lycoris, Senega, OC. kudzuvine root, fritillary bulb, gambir, fennel, Scutellaria root, trichosanthes Seed, cinnamon bark, oriental beZoar, 0029. The amount of the vitamin is determined based on Schisandra fruit, asiasarum root, tatarian aster root, musk, the type and amount of other medicines used in combination codonopsis root, ginger, mulberry bark, perilla herb, panax according to a known formulation technique. A dose for an rhizome, citrus unshiu peel, ginseng, ophiopogon tuber, and adult is usually 0.1-2,000 mg/day, and preferably 1-500 pinelia tuber, and their extracts. These can be used either mg/day. individually or in combination of two or more. 0030 Examples of the antiinflammatory enzyme include bromelain, pronase, Serrapeptase, Semialkaline proteinase, 0022. The amount of the galenical is determined based on Streptokinase, Streptodornase, and lysozyme chloride. These the type and amount of other medicines used in combination according to a known formulation technique. A dose for an can be used either individually or in combination of two or adult is usually 0.001-300 g/day (as an extract, converted OC. into the raw galenical) or 0.0004-60 g/day (as a powder), and 0031. A dose for an adult of the antiinflammatory enzyme preferably 0.005-10 g/day (as an extract, converted into the is usually 4-300 mg/day, and preferably 15-60 mg/day. raw galenical) or 0.001-3 g/day (as a powder). 0032 Expectorants other than fudosteine such as potas 0023 Examples of the antacid or mucosal protective sium guaiacolsulfonate, guaifenesin, potassium iodide, foe agent include aminoacetic acid, magnesium oxide, magne niculated ammonia Spirit, Sodium hydrogencarbonate, bro sium carbonate, magnesium Silicate, Synthetic aluminum mhexine hydrochloride, carbocysteine, ambroXol Silicate, Synthetic hydrotalcite, dihydroaluminum aminoac hydrochloride, methylcysteine hydrochloride, acetylcys etate, aluminum hydroxide gel, aluminum hydroxide dried teine, ethylcysteine hydrochloride, eprazinone hydrochlo US 2004/O147605 A1 Jul. 29, 2004

ride, ammonium chloride, potassium creSolsulfonate, 1-men 0038. Usually, a liquid preparation for internal use such thol, trimetoquinol hydrochloride, phenylpropanolamine as a Syrup preparation, elixir preparation, limonade prepa hydrochloride, and methoxyphenamine hydrochloride, for ration, extract preparation, or drink preparation, as well as a example, may be added to the drug preparation of the hard capsule preparation, Soft capsule preparation, or the present invention individually or in combination of two or like in which a liquid or Semisolid Substance is capsuled, can OC. be produced by a method wherein the medicinal components are mixed with, dissolved in, or dispersed in a part of a 0033. A dose for an adult of these expectorants is usually Solvent Such as purified water, followed by adjusting the 1-3,000 mg/day, and preferably 6-900 mg/day. liquid amount by adding the remaining part of the Solvent to 0034. The drug preparation of the present invention is the mixture. The pH may be appropriately adjusted using an prepared by appropriately combining the above-described acid or alkali. The preparation containing a fat-Soluble components with a pharmaceutically acceptable additive component may be Solubilized, emulsified, or Suspended into a Solid, Semisolid, or liquid preparation to be orally using an additive Such as a Surfactant, Solubilizer, emulsifier, administered Such as a tablet preparation, granule prepara or Suspending agent. AS required, the mixture may be tion, fine granule preparation, powder preparation, hard heated, cooled, replaced with nitrogen, filtered, or Sterilized capsule preparation, Soft capsule preparation, pellet prepa during the adjustment. ration, troche preparation, drop preparation, Suspension preparation, emulsion preparation, liquid preparation for 0039 The drug preparation of the present invention may internal use, Syrup preparation, dry syrup preparation, inhal be appropriately provided with properties Such as Stability, ant preparation, or oral mucoadhesive preparation, accord Sustained releasability, durability, or capability of rapid ing to a conventional method. The medicinal components disintegration or rapid dissolution of the medicinal compo may be made into microparticles Such as microcapsules, nents, improved Solubility, taste masking properties, and nanocapsules, microSpheres, or nanospheres prior to prepar capability of imparting improved feeling during the dosing, using an additive or the like. A conventional method can be ing the above-mentioned preparation. used for providing these properties. Examples of the method 0035. There are no specific limitations to the method for include various methods Such as a method of adding the preparing the drug preparation of the present invention. medicinal components to Separate granules, a method of Various methods can be employed. For example, when it is preparing multilayer granules from the components, a necessary to prepare a granulated powder for preparing a method of preparing multilayer tablets or core tablets from tablet preparation, granule preparation, fine granule prepa the components, a method of preparing Separate granules ration, powder preparation, capsule preparation, pellet from the components and tableting them, a method of preparation, dry Syrup preparation, or the like, conventional preparing microcapsules from the components, a method of granulation is employed. Examples of the granulation preparing a coated preparation Such as Sugar-coated tablets, include wet granulation using a Solution or dispersion liquid film-coated tablets, or coated granules from the components, containing water or an organic Solvent Such as Spray granu a method of preparing an effervescent preparation from the lation, agitating granulation, fluidized bed granulation, roll components, a method of preparing a chewable preparation ing granulation, or rolling fluidized bed granulation and dry from the components, a method of preparing an orally granulation using a powdery binder Such as compression disintegrating preparation from the components, a method of granulation. preparing a matrix preparation from the components, a 0036) A powder or granulated powder containing the method of pulverizing the components all together, a method medicinal components can be mixed and packed into a of preparing a Solid Solution from the components, a method plurality of packages to prepare a granule preparation, fine of adding a Sweetener or cooling agent to the components, granule preparation, or powder preparation. A powder prepa a method of adding an antioxidant or Stabilizer to the ration, granulated powder, Small tablet preparation, or the components, and a method of adjusting the composition to like is capsuled using a capsuling machine to prepare a have a specific pH, Viscosity, osmotic preSSure, or Salt capsule preparation. A powder of the medicinal components, concentration. These methods may be used in combination. powder preparation, fine granule preparation, granule prepa 0040 AS pharmaceutically acceptable additives used in ration, or pellet preparation is mixed with an additive and the the drug preparation of the present invention, a Stabilizer, mixture is compression molded to prepare a tablet prepara Surfactant, plasticizer, lubricant, Solubilizer, reductant, tion. buffer, Sweetener, base, adsorbent, flavor enhancer, binder, Suspending agent, antioxidant, brightener, coating agent, 0037. A tablet preparation, granule preparation, or the humectant, filler, antifoaming agent, cooling agent, colorant, like is coated with a coating agent using pan coating, Odorant, flavor, Sugar-coating agent, isotonizing agent, Soft fluidized bed coating, roll coating, or a combination of these, ener, emulsifier, thickener, effervescent agent, pH adjuster, to prepare a coated preparation Such as Sugar-coated tablets, diluent, and other additives Such as an excipient, dispersant, film-coated tablets, or coated granules. The coating agent disintegrant, disintegrating assistant, disintegration retar may be applied by Spray coating wherein the agent is dant, perfume, desiccant, antiseptic, preservative, dissolving dissolved and/or dispersed in water or an organic Solvent or dry coating wherein the agent is directly sprayed and heat, agent, dissolving assistant, Solvent, fluidizer, antistatic preSSure, or the like is applied. The amount of the coating agent, extender, moisture retainer, and moisturizer can be agent can be appropriately Selected according to the dosage given. More Specifically, the following additives can be form or the like. The amount is usually about 0.1-100 weight given. These can be used either individually or in combi % for a tablet preparation, about 0.1-200 weight % for a nation of two or more. pellet or granule preparation, or about 0.1-300 weight % for 0041) Specific examples of the excipient, base, or filler a fine granule preparation. include DL-alanine, dl-malic acid, D-Sorbitol, D-Sorbitol US 2004/O147605 A1 Jul. 29, 2004

Solution, D-mannitol, L-aspartic acid, L-glutamine, B-cyclo Snake oil, tartaric acid, potassium hydrogen tartrate, heavy dextrin, aminoethylsulfonic acid, powdered Starch Syrup, Silicic anhydride, flour, wheat germ oil, ethanol for disin gum arabic, gum arabic powder, alginic acid, Sodium algi fection, calcined gypsum, calcium acetate, cellulose acetate nate, propylene glycol alginate, pregelatinized Starch, inosi phthalate, Starch Syrup, magnesium aluminum hydroxide, tol, ethanol, ethyl cellulose, octyldecyl triglyceride, opadry aluminum hydroxide-magnesium carbonate-calcium car beige, olive oil, oleic acid, kaolin, cacao butter, casein, bonate coprecipitate, aluminum hydroxide-Sodium, hydro Sodium caseinate, carrageenan, caramel, carnauba wax, car gencarbonate coprecipitate, aluminum hydroxide gel, mag boxyvinyl polymer, Sodium carboxymethyl Starch, carmel nesium hydroxide, hydrogenated vegetable oil, physiological Saline Solution, purified gelatin, purified shel lose, carmellose calcium, carmellose Sodium, glycyrrhiza lac, purified honey, purified water, purified Sucrose, purified powder, agar, agar powder, Xanthan gum, Xylytol, citric acid, Sucrose Spherical granules, Soybean lecithin, unsaponified Sodium citrate, disodium citrate, glycine, glycerol, glycerol Soybean oil, tricalcium phosphate, skim milk powder, Simple fatty acid ester, calcium gluconate, Sodium gluconate, cros Syrup, ammonium carbonate, calcium carbonate, magne carmellose Sodium, croSpoVidone, cinnamon bark powder, sium carbonate, medium-chain triglyceride, precipitated cal magnesium alumino Silicate, calcium Silicate, magnesium cium carbonate, low-Substituted Sodium carboxymethyl Silicate, brown rice malt, Succinated gelatin, Sesame oil, Starch, low-Substituted hydroxypropyl cellulose, natural alu wheat Starch, wheat germ powder, rice Starch, cholesterol, minum Silicate, Silicon dioxide, lactic acid, calcium lactate, Safflower oil, white beeswax, dihydroxyaluminum aminoac lactose, lactose particles, concentrated glycerol, white shel etate, dimethylpolysiloxane (for internal use), Sucrose fatty lac, Sucrose, Sucrose-starch Spherical granules, half-digested acid ester, Stearyl alcohol, Stearic acid, calcium Stearate, Starch, microcrystalline cellulose, partially pregelatinized polyoxyl 40 Stearate, magnesium Stearate, Zein, Sorbitan Starch, powder Sugar, cellulose powder, hydrogenated mal Sesquioleate, cetanol, gypsum, gelatin, Sorbitan fatty acid tose powder Starch Syrup, rice powder, citric anhydride, ester, hydrogenated Soybean oil, Soybean oil, talc, dextran hydrated Silicic anhydride, anhydrous calcium hydrogen 40, dextrin, Sodium dehydroacetate, calcium glycerophoS phosphate, anhydrous calcium hydrogen phosphate gran phate, corn Syrup, corn Starch, corn Starch granules, traga canth, tragacanth powder, triacetin, rapeseed oil, pearl pow ules, anhydrous lactose, anhydrous Sodium Sulfate, Sterilized der, powdered juice from green barley leaves, honey, purified water, cotton Seed oil, cotton Seed oil-Soybean oil paraffin, potato Starch, bitter chocolate, hydroxypropyl mixture, medicinal charcoal, liquid paraffin, calcium Sulfate, Starch, hydroxypropyl cellulose, hydroxypropyl methylcel and green tea powder. lulose 2208, hydroxypropyl methylcellulose 2906, hydrox 0042 Specific examples of the solvent, solubilizer, dis ypropyl methylcellulose 2910, hydroxypropyl methylcellu Solving agent, or dissolving assistant include dl-camphor, lose phthalate, castor oil, Sunflower oil, phytin acid, D-mannitol, D-Sorbitol, D-Sorbitol Solution, L-aspartic acid, phenacetin, glucose, hydrous glucose, pullulan, propylene L-arginine, C-cyclodextrin, 3-cyclodextrin, adipic acid, fen glycol, propylene glycol fatty acid ester, pectin, bentonite, nel oil, esterified corn oil, ethanol, olive oil, oleic acid, oleyl poVidone, Sodium polyacrylate, partially neutralized poly oleate, carmelloSe Sodium, citric acid, Sodium citrate, gly acrylic acid, polyisobutylene, polyoxyethylene (105) poly cine, glycerol, glycerol fatty acid ester, Sesame oil, Safflower oxypropylene (5) glycol, polyoxyethylene (160) polyox oil, Safflower oil fatty acid, Sodium Salicylate, perilla oil, ypropylene (30) glycol, polyoxyethylene hydrogenated dibutylhydroxytoluene, Sucrose fatty acid ester, Stearyl alco castor oil, polyoxyethylene hydrogenated castor oil 40, hol, polyoxyl 40 Stearate, Sorbitan Sesquioleate, Sorbitan polyoxyethylene hydrogenated castor oil 60, Sodium poly fatty acid ester, Soybean oil, Sodium dehydroacetate, corn styrene Sulfonate, polysorbate 60, polysorbate 80, polyvinyl oil, triacetin, Sorbitan trioleate, tricapryline, rapeseed oil, acetal diethylaminoacetate, (partially Saponified) polyvinyl nicotinamide, peppermint oil, hydroxypropyl cellulose, alcohol, polyvinyl alcohol-diethylene glycol mixture, oyster hydroxypropyl methylcellulose 2910, castor oil, phen shell powder, macrogol 1500, macrogol 1540, macrogol probamate, glucose, propylene glycol, propylene glycol 20000, macrogol 300, macrogol 400, macrogol 4000, mac fatty acid ester, povidone, polyoxyethylene (105) polyox rogol 6000, multitol, yellow beeswax, myristyl alcohol, ypropylene (5) glycol, polyoxyethylene (160) polyoxypro octyldodecyl myristate, methacrylic acid copolymer LD, pylene (30) glycol, polyoxyethylene hydrogenated castor magnesium aluminometasilicate, methyl acrylate-meth oil, polyoxyethylene hydrogenated castor oil 40, polyoxy acrylic acid copolymer, methyl cellulose, Japan wax, alu ethylene hydrogenated castor oil 60, polySorbate 20, minum monoStearate, glycerol monoStearate, Sodium lauryl polySorbate 60, polySorbate 80, (partially Saponified) poly Sulfate, lauromacrogol, peanut oil, calcium monohydrogen vinyl alcohol, macrogol 1500, macrogol 200, macrogol 300, phosphate, calcium hydrogen phosphate, calcium hydrogen macrogol 400, macrogol 4000, macrogol 600, macrogol phosphate particles, Sodium hydrogen phosphate, potassium 6000, maleic acid, isopropyl myristate, Sorbitan monooleate, dihydrogen phosphate, calcium dihydrogen phosphate, Sorbitan monolaurate, coconut oil, Sodium lauryl Sulfate, Sodium dihydrogen phosphate, rose oil, rosin, Sodium chlo lauromacrogol, peanut oil, lidocaine, Ringer's Solution, ride, fructose, dry chlorella, dry yeast, dried aluminum phosphoric acid, Sodium hydrogen phosphate, potassium hydroxide gel, dry magnesium Sulfate, baked rice cake dihydrogen phosphate, Sodium benzoate, benzyl benzoate, powder, hydrogenated maltose Starch Syrup, hydrous Silicon Sodium chloride, magnesium chloride, dry Sodium carbon dioxide, hydrous amorphous Silicon oxide, light Silicic anhy ate, diluted hydrochloric acid, argentine, hydrogenated oil, dride, light liquid paraffin, whale wax, crystalline cellulose, magnesium oxide, tartaric acid, wheat germ oil, ethanol for crystalline cellulose (particles), crystalline cellulose (fine disinfection, water, acetic acid, cellulose acetate phthalate, particles), crystalline cellulose-carmellose Sodium, hydro Sodium hydroxide, physiological Saline Solution, purified genated oil, Synthetic aluminum Silicate, Synthetic alumi Soybean oil, purified water, purified Soybean lecithin, petro num Silicate-hydroxypropyl Starch-crystalline cellulose, leum benzine, Soybean lecithin, Sodium carbonate, Sodium Synthetic hydrotalcite, titanium oxide, magnesium oxide, hydrogen carbonate, medium-chain triglyceride, low-Substi US 2004/O147605 A1 Jul. 29, 2004 tuted hydroxypropyl cellulose, lactic acid, dark glycerol, mide, glucose, monosodium fumarate, propylene glycol, Sucrose, glacial acetic acid, anhydrous ethanol, citric anhy Sodium polyphosphate, macrogol 4000, maleic acid, Sodium dride, maleic anhydride, anhydrous Sodium monohydrogen metaphosphate, phosphoric acid, dipotassium phosphate, phosphate, Sterilized purified water, cotton Seed oil, and triSodium phosphate, Sodium hydrogen phosphate, potas liquid paraffin. sium dihydrogen phosphate, Sodium dihydrogen phosphate, 0.043 Specific examples of the disintegrant, disintegrat rose oil, benzoic acid, Sodium benzoate, potassium chloride, ing assistant, dispersant, desiccant, or fluidizer include calcium chloride, Sodium chloride, magnesium chloride, D-Sorbitol, D-mannitol, adipic acid, aminoalkyl methacry hydrochloric acid, glucosamine hydrochloride, fructose, dry late copolymer RS, gum arabic, gum arabic powder, alginic Sodium Sulfite, dry Sodium carbonate, diluted hydrochloric acid, Sodium alginate, propylene glycol alginate, pregelati acid, tartaric acid, acetic acid, Sodium hydroxide, magne nized Starch, ethanol, ethyl cellulose, olive oil, oleic acid, sium hydroxide, physiological Saline Solution, Sodium car carboxyvinyl polymer, Sodium carboxymethyl Starch, car bonate, Sodium hydrogen carbonate, lactic acid, calcium mellose, carmellose calcium, carmellose Sodium, glycyr lactate, lactose, concentrated glycerol, glacial acetic acid, rhiza powder, agar powder, guar gum, citric acid, calcium citric anhydride, anhydrous Sodium citrate, anhydrous citrate, Sodium citrate, glycerol, glycerol fatty acid ester, Sodium pyrophosphate, anhydrous Sodium monohydrogen croScarmelloSe Sodium, crospoVidone, magnesium Silicate, phosphate, anhydrous trisodium phosphate, anhydrous dihy wheat Starch, rice Starch, choline phosphate, Safflower oil, drogen phosphate, and Sodium hydrogen Sulfate. white beeswax, dioctyl Sodium SulfoSuccinate, Sucrose fatty 004.5 Specific examples of the surfactant, emulsifier, or acid ester, Stearic acid, calcium Stearate, polyoxyl 40 Stear effervescent agent include D-Sorbitol, ethanol, carrageenan, ate, magnesium Stearate, Sorbitan Sesquioleate, gelatin, Sor carboxyvinyl polymer, carmelloSe Sodium, guar gum, glyc bitan fatty acid ester, talc, Soybean oil, dextrin, corn Starch, erol, glycerol fatty acid ester, cholesterol, white beeswax, tragacanth powder, Sorbitan trioleate, honey, paraffin, potato dioctyl Sodium SulfoSuccinate, Sucrose fatty acid ester, starch, hydroxyethyl cellulose, hydroxyethyl methylcellu Stearyl alcohol, Stearic acid, polyoxyl 40 Stearate, Sorbitan lose, hydroxypropyl Starch, hydroxypropyl cellulose, Sesquioleate, cetanol, gelatin, Sorbitan fatty acid ester, talc, hydroxypropyl methylcellulose 2910, hydroxypropyl meth Sorbitan trioleate, paraffin, potato Starch, hydroxypropyl ylcellulose 2910 mixture, castor oil, fumaric acid, monoSo cellulose, propylene glycol, propylene glycol fatty acid dium fumarate, propylene glycol, propylene glycol fatty acid ester, pectin, polyoxyethylene (105) polyoxypropylene (5) ester, bentonite, povidone, polyoxyethylene (105) polyox glycol, polyoxyethylene (160) polyoxypropylene (30) gly ypropylene (5) glycol, polyoxyethylene (160) polyoxypro col, polyoxyethylene hydrogenated castor oil, polyoxyeth pylene (30) glycol, polyoxyethylene hydrogenated castor ylene hydrogenated castor oil 40, polyoxyethylene hydro oil, polyoxyethylene hydrogenated castor oil 60, polyoxy genated castor oil 60, polyoxyl 35 castor oil, polySorbate 20, ethylene hydrogenated castor oil 40, polySorbate 20, polysorbate 60, polysorbate 80, macrogol 400, octyldodecyl polysorbate 40, polysorbate 60, polysorbate 80, polyvinyl myristate, methyl cellulose, Sorbitan monooleate, glycerol acetal diethylaminoacetate, Sodium polyphosphate, mac monoStearate, Sorbitan monopalmitate, Sorbitan monolau rogol 1500, macrogol 300, macrogol 400, macrogol 4000, rate, lauryl dimethylamine oxide Solution, Sodium lauryl macrogol 6000, magnesium aluminometasilicate, Sodium Sulfate, lauromacrogol, dry Sodium carbonate, tartaric acid, metaphosphate, methyl cellulose, Japan wax, Sorbitan Sodium hydroxide, purified Soybean lecithin, Soybean leci monooleate, aluminum monoStearate, glycerol monoStear thin, potassium carbonate, Sodium hydrogen carbonate, ate, Sorbitan monopalmitate, Sorbitan monolaurate, Sodium medium-chain triglyceride, citric anhydride, cotton Seed lauryl Sulfate, lauromacrogol, calcium hydrogen phosphate, oil-Soybean oil mixture, and liquid paraffin. calcium hydrogen phosphate granules, calcium dihydrogen 0046) Specific examples of the humectant, binder, Sus phosphate, dried aluminum hydroxide gel, light aluminum pending agent, thickener, adhesive, adhesion enhancer, Soft oxide, light Silicic anhydride, crystalline cellulose, crystal ener, or plasticizer include D-Sorbitol, D-Sorbitol Solution, line cellulose-carmellose Sodium, hydrogenated oil, hydrous D-mannitol, RSS No. 1 crude rubber, B-captan, B-cyclodex Silicon dioxide, Synthetic aluminum Silicate, titanium oxide, trin, acrylic acid-octyl acrylate copolymer, 2-ethylhexyl Sodium dehydroacetate, heavy Silicic anhydride, Vinyl acrylate-Vinyl pyrrolidone copolymer Solution, 2-ethylhexyl acetate resin, cellulose acetate phthalate, magnesium alumi acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate num hydroxide, Sodium hydroxide, purified shellac, purified copolymer Solution, acrylic ester-Vinyl acetate copolymer, Soybean lecithin, purified Sucrose, Soybean lecithin, trical ethyl acrylate-methyl methacrylate copolymer dispersion cium phosphate, magnesium carbonate, Sodium hydrogen liquid, acetyl glycerol fatty acid ester, acrylic acid-Silk carbonate, precipitated calcium carbonate, low-Substituted fibroin copolymer resin, methyl acrylate-2-ethylhexyl acry Sodium carboxymethyl Starch, low-Substituted hydroxypro late copolymer resin emulsion, acrylic resin alkanolamine pyl cellulose, lactose, concentrated glycerol, white shellac, Solution, magnesium Stearate, aminoalkyl methacrylate Sucrose, partially pregelatinized Starch, anhydrous ethanol, copolymer E, aminoalkyl methacrylate copolymer RS, ami citric anhydride, anhydrous Sodium citrate, anhydrous noethylsulfonic acid, amylopectin, powdered Starch Syrup, Sodium pyrophosphate, and liquid paraffin. gum arabic, gum arabic powder, Sodium alginate, propylene 0044 Specific examples of the pH adjuster, isotonizing glycol alginate, pregelatinized Starch, ester gum, ethanol, agent, or buffer includedl-malic acid, D-Sorbitol, D-Sorbitol ethyl cellulose, Sodium erythorbate, phellodendron bark, Solution, D-mannitol, D-tartaric acid, magnesium L-aspar olive oil, Sodium oleate, kaolin, cacao butter, Sodium casein tate, L-arginine, L-glutamic acid, Sodium L-glutamate, adi ate, carrageenan, caramel, carnauba wax, carboxyvinyl pic acid, ascorbic acid, aminoethylsulfonic acid, Xylytol, polymer, carboxy vinyl polymer, carboxymethyl ethylcellu citric acid, calcium citrate, Sodium citrate, disodium citrate, lose, Sodium carboxymethyl Starch, carmellose, carmellose glycine, glycerol, glucono-Ö-lactone, calcium gluconate, calcium, carmellose Sodium, agar, agar powder, Xanthan Succinic acid, disodium Succinate hexahydrate, nicotina gum, benzyl acetate, guar gum, Sodium citrate, glycine, US 2004/O147605 A1 Jul. 29, 2004 glycerol, glycerol fatty acid ester, glucono-6-lactone, mag Simple Syrup, calcium carbonate, magnesium carbonate, nesium Silicate, magnesium aluminum Silicate, copal resin, medium-chain triglyceride, precipitated calcium carbonate, copolyVidone, Sesame oil, wheat Starch, rice Starch, collo low Substituted hydroxypropyl cellulose, lactic acid, lactose, dion, Sodium chondroitin Sulfate, white beeswax, dioctyl concentrated glycerol, white shellac, white petrolatum, Sodium SulfoSuccinate, cispolyisoprene rubber, dihydroxy Sucrose, microcrystalline cellulose, partially pregelatinized aluminum aminoacetate, dibutylhydroxytoluene, dimeth Starch, rice powder, anhydrous ethanol, cotton Seed oil ylpolysiloxane (for internal use), dimethylpolysiloxane-sili Soybean oil mixture, liquid paraffin, calcium Sulfate, and con dioxide mixture, Sucrose fatty acid ester, Stearyl alcohol, Sulfated castor oil potassium Salt-alkylbenzeneSulfonic acid Stearic acid, aluminum Stearate, calcium Stearate, polyoxyl mixture. Stearate, polyoxyl 40 Stearate, Styrene-isoprene-Styrene 0047 Specific examples of the coating agent, Sugar block copolymer, Styrene isoprene rubber, Sorbitan Sesqui coating agent, brightener, or antifoaming agent include oleate, cetanol, gelatin, shellac, Sorbitan fatty acid ester, 2-methyl-5-vinylpyridinemethyl acrylate-methacrylic acid Solvent naphtha, Soybean hydrogenated oil, talc, dammar copolymer, dl-malic acid, D-Sorbitol, D-Sorbitol Solution, gum, dextran 70, dextrin, terpene resin, (Soluble) starch, D-mannitol, ethyl acrylate-methyl methacrylate copolymer corn Starch, corn oil, tragacanth, tragacanth powder, Sorbitan dispersion liquid, acetylglycerol fatty acid ester, aminoalkyl trioleate, rapeseed oil, high cispolyisoprene rubber molecu methacrylate copolymer E, aminoalkyl methacrylate lar weight: 47,000, honey, paraffin, potato Starch, Veegum copolymer RS, gum arabic, gum arabic powder, purified neutral, hydroxyethyl cellulose, hydroxyethyl methylcellu insect wax, ethanol, ethyl cellulose, ethyl cellulose water lose, hydroxypropyl Starch, hydroxypropyl cellulose, dispersion, octyldecyl triglyceride, Opadry OY-6950, hydroxypropyl methylcellulose 2208, hydroxypropyl Opadry OY-S-22829, Opadry OY-S-22835, Opadry OY-S- methyl cellulose 2906, hydroxypropyl methyl cellulose 22961, Opadry OY-S-7135, Opadry OY-S-8471, Opadry 2910, hydroxypropyl methylcellulose acetate Succinate, OY-S-9607, olive oil, kaolin, cacao butter, prunella spike, hydroxypropyl methylcellulose phthalate, Vinyl pyrroli hydrogenated castor wax, caramel, carnauba wax, carbox done-Vinyl acetate copolymer, piperonyl butoxide, castor yvinyl polymer, carboxymethyl ethylcellulose, Sodium car oil, glucose, fumaric acid, fumaric acid-Stearic acid-polyvi boxymethyl Starch, carmellose calcium, carmellose Sodium, nyl acetal diethylaminoacetate-hydroxypropyl methylcellu triethyl citrate, glycerol, glycerol fatty acid ester, magne lose 2910 mixture, Sodium Stearyl fumarate, pullulan, pro sium Silicate, Succinated gelatin, wheat Starch, rice Starch, pylene glycol, propylene glycol fatty acid ester, pectin, white beeswax, dimethylaminoethyl methacrylate-methyl bentonite, povidone, polyacrylic acid, sodium polyacrylate, methacrylate copolymer, dimethylpolysiloxane (for internal polyacrylic aqueous Solution, partially neutralized poly use), dimethylpolysiloxane-Silicon dioxide mixture, Sucrose acrylic acid, polyisobutylene, polyoxyethylene (160) poly fatty acid ester, Silicone resin emulsion, Silicone antifoaming oxypropylene (30) glycol, polyoxyethylene hydrogenated agent, eaglewood powder, Stearyl alcohol, Stearic acid, alu castor oil, polyoxyethylene hydrogenated castor oil 60, minum Stearate, calcium Stearate, polyoxyl 40 Stearate, polysorbate 20, polysorbate 60, polysorbate 80, polysorbate magnesium Stearate, Zein, Sorbitan Sesquioleate, cetanol, 80-polyvinyl acetal diethylaminoacetate, (entirely Saponi gypsum, shellac, Sorbitan fatty acid ester, talc, terpene resin, fied) polyvinyl alcohol, (partially Saponified) polyvinyl alco (Soluble) starch, corn Syrup, corn oil, triacetin, Sorbitan hol, polybutene, Sodium polyphosphate, macrogol 1500, trioleate, pearl powder, honey, paraffin, potato Starch, macrogol 20000, macrogol 300, macrogol 400, macrogol hydroxypropyl cellulose, hydroxypropyl methylcellulose 4000, macrogol 600, macrogol 6000, maleic rosinglycerol 2208, hydroxypropyl methylcellulose 2906, hydroxypropyl ester, yellow beeswax, methacrylic acid-n-butyl acrylate methylcellulose 2910, hydroxypropyl methylcellulose 2910 copolymer, methacrylic acid copolymer L, methacrylic acid titanium oxide-macrogol 400 mixture, hydroxypropyl meth copolymer LD, methacrylic acid copolymer S, magnesium ylcellulose acetate Succinate, hydroxypropyl methylcellu aluminometasilicate, Sodium metaphosphate, methyl cellu lose phthalate, piperonyl butoxide, castor oil, diethyl lose, methyl Vinyl ether-maleic anhydride copolymer, Japan phthalate, butylphthalyl butylglycolate, glucose, fumaric wax, glycerol monoStearate, Sodium lauryl Sulfate, lauro acid-Stearic acid-polyvinyl acetal diethylaminoacetate-hy macrogol, peanut oil, phosphoric acid, calcium hydrogen droxypropyl methylcellulose 2910 mixture, pullulan, pro phosphate, rosin, calcium chloride, Sodium chloride, mag pylene glycol, bentonite, povidone, polyoxyethylene (105) nesium chloride, hydrous lanolin, hydrolyzed gelatin pow polyoxypropylene (5) glycol, polyoxyethylene (160) poly der, hydrolyzed Starch-added light Silicic anhydride, fruc oxypropylene (30) glycol, polyoxyethylene hydrogenated tose, dried aluminum hydroxide gel, baked rice cake castor oil 40, polyoxyethylene hydrogenated castor oil 60, powder, hydrogenated Starch Syrup, hydrous Silicon dioxide, polySorbate 80, polyvinyl acetal diethylaminoacetate, (par hydrous amorphous Silicon oxide, light Silicic anhydride, tially Saponified) polyvinyl alcohol, macrogol 1500, mac light Silicic anhydride-containing hydroxypropyl cellulose, rogol 1540, macrogol 20000, macrogol 300, macrogol light liquid paraffin, crystalline cellulose, crystalline cellu 35000, macrogol 400, macrogol 4000, macrogol 600, mac lose-carmellose Sodium, hydrogenated oil, high polyvinyl rogol 6000, yellow beeswax, myristyl alcohol, methacrylic pyrrollidone, Synthetic aluminum Silicate, Synthetic wax, acid copolymer L, methacrylic acid copolymer LD, meth titanium oxide, magnesium oxide, alicyclic Saturated hydro acrylic acid copolymer S, magnesium aluminometasilicate, carbon resin, aliphatic hydrocarbon resin, Sodium potassium methyl cellulose, Japan wax, aluminum monoStearate, glyc tartrate, heavy Silicic anhydride, flour, water, Vinyl acetate erol monoStearate, Sorbitan monolaurate, montanic acid resin, cellulose acetate phthalate, Starch Syrup, aluminum ester wax, Sodium lauryl Sulfate, lauromacrogol, calcium hydroxide gel, potassium hydroxide, Sodium hydroxide, monohydrogen phosphate, calcium hydrogen phosphate, hydrogenated rosin glycerol ester, crude rubber, purified Sodium hydrogen phosphate, calcium dihydrogen phospho gelatin, purified Shellac, purified water, purified Sucrose, ate, rosin, dry methacrylic acid copolymer LD, dried alu petroleum benzine, petroleum resin, Soybean lecithin, minum hydroxide gel, dry bleached shellac, baked rice cake US 2004/O147605 A1 Jul. 29, 2004

powder, hydrous Silicon dioxide, argentine, gold foil, Silver oxide, tartaric acid, acetic acid, tocopherol acetate, Sodium foil, light Silicic anhydride, light liquid paraffin, light Silicic hydroxide, magnesium hydroxide, purified gelatin, purified anhydride-containing hydroxypropyl cellulose, whale wax, Soybean lecithin, purified Sucrose, dried aluminum hydrox crystalline cellulose, hydrogenated wax, hydrogenated oil, ide gel, Soybean lecithin, unsaponified Soybean oil, potas high glucose Starch Syrup, Synthetic aluminum Silicate, sium carbonate, Sodium carbonate, magnesium carbonate, Synthetic wax, titanium oxide, magnesium oxide, flour, potassium hydrogen carbonate, Sodium hydrogen carbonate, calcined gypsum, cellulose acetate, vinyl acetate resin, cel nitrogen, natural Vitamin E, lactic acid, lactose, concentrated lulose acetate phthalate, Starch Syrup, aluminum hydroxide glycerol, Sucrose, microcrystalline cellulose, glacial acetic gel, hydrogenated rosinglycerol ester, purified gelatin, puri acid, propyl gallate, citric anhydride, anhydrous Sodium fied shellac, purified paraffin-carnauba wax mixed wax, citrate, anhydrous Sodium pyrophosphate, anhydrous purified Sucrose, tricalcium phosphate, Simple Syrup, cal Sodium monohydrogen phosphate, medicinal charcoal, and cium carbonate, magnesium carbonate, discolored Silver ovalbumin. foil, precipitated calcium carbonate, low-Substituted hydrox ypropyl cellulose, calcium lactate, lactose, concentrated 0049 Specific examples of the flavor enhancer, cooling glycerol, white shellac, Sucrose, partially pregelatinized agent, perfume, or Sweetener include disodium 5'-inosinate, Starch, powder Sugar, hydrated Silicic anhydride, phthalic disodium 5-guanylate, DL-alanine, dl-camphor, d1-menthol, anhydride, anhydrous calcium hydrogen phosphate, medici dl-malic acid, Sodium dl-malate, Sodium DL-tartarate, nal charcoal, liquid paraffin, and calcium Sulfate. d-camphor, D-xylose, D-Sorbitol, D-Sorbitol solution, d-borneol, D-mannitol, D-tartaric acid, L-aspartic acid, 0.048 Specific examples of the stabilizer, antioxidant, Sodium L-aspartate, magnesium L-aspartate, L-glutamic preservative, or antiseptic include adipic acid, DL-alanine, acid, L-arginine L-glutamate, Sodium L-glutamate, dl-camphor, D-Sorbitol solution, d-borneol, D-Sorbitol, L-glutamic acid hydrochloride, 1-menthol, B-cyclodextrin, D-mannitol, L-ascorbyl Stearate, Sodium L-ascorbate, L-as ascorbic acid, aspartame, gambir powder, Sweet hydrangea partic acid, Sodium L-aspartate, L-arginine, 1-menthol, B-cy leaf, Sweet hydrangea leaf extract, Sweet hydrangea leaf clodextrin, ascorbic acid, aminoethylsulfonic acid, Sodium powder, aminoethylsulfonic acid, fennel, fennel tincture, alginate, propylene glycol alginate, albumin, Sulfur, inositol, fennel powder, fennel oil, ethanol, ethyl Vanillin, erythritol, fennel powder, ethanol, calcium disodium edetate, Sodium phellodendron bark powder, Japanese cherry bark extract, edetate, erythorbic acid, Sodium erythorbate, cacao butter, coptis rhizome, coptis rhizome powder, Ononis root drying carboxyvinyl polymer, carmellose calcium, carmellose extract, orange, orange oil, cacao powder, caramel, carba Sodium, agar, Xanthan gum, Xylytol, citric acid, calcium chol, glycyrrhiza, glycyrrhiza extract, crude glycyrrhiza citrate, Sodium citrate, glycine, glycerol, glycerol fatty acid extract, glycyrrhiza powder, Xylytol, citric acid, calcium ester, glucono-Ö-lactone, calcium gluconate, cinnamon bark citrate, Sodium citrate, glycine, glycerol, glycyrrhizinic acid, powder, Sesame oil, Sodium chondroitin Sulfate, Salicylic diammonium glycyrrhizinate, dipotassium glycyrrhizinate, acid, Sodium Salicylate, phenyl Salicylate, dibutylhydroxy disodium glycyrrhizinate, monoammonium glycyrrhizinate, toluene, Sucrose fatty acid ester, Stearic acid, aluminum triSodium glycyrrhizinate, glucono-6-lactone, chlorella Stearate, polyoxyl Stearate, magnesium Stearate, Sorbitan extract, chlorella powder, cinnamon bark tincture, cinnamon Sesquioleate, cetanol, gelatin, Sorbitan fatty acid ester, Sorbic bark powder, cinnamon bark oil, Succinic acid, disodium acid, potassium Sorbate, talc, dextran, dextran 40, dextran Succinate hexahydrate, monosodium Succinate, Seaweed 70, dehydroacetic acid, Sodium dehydroacetate, disodium powder, Saccharin, Saccharin Sodium, Saffron powder, Saf glycyrrhizinate, tocopherol, menthol, naphtol, nicotinamide, frontincture, Zanthoxylum peel tincture, Zanthoxylum peel honey, isobutyl p-hydroxybenzoate, isopropyl p-hydroxy powder, amomum Seed powder, ginger tincture, ginger pow benzoate, ethyl p-hydroxybenzoate, butyl p-hydroxyben der, ginger oil, eaglewood powder, cinnamaldehyde, Stearic Zoate, propyl p-hydroxybenzoate, methyl p-hydroxyben acid, Spearmint oil, Swertia herb, perilla herb powder, Soy Zoate, calcium pantotheate, hydroxypropyl cellulose, bean oil, jujube powder, alisma rhizome root/herb dry hydroquinone, tetrasodium pyrophosphate, Sodium pyro extract, tannic acid, clove tincture, clove oil, citrus unshiu Sulfite, phenacetin, butylhydroxyanisol, glucose, fumaric peel tincture, red pepper, red pepper powder, red pepper acid, monosodium fumarate, poVidone, partially neutralized tincture, bitter orange peel tincture, bitter orange peel pow polyacrylic acid, polyoxyethylene (160) polyoxypropylene der, picrasma wood powder, pineapple powder flavor 51357, (30) glycol, polyoxyethylene hydrogenated castor oil 60, pineapple powder flavor 59492, honey, peppermint water, polysorbate 20, polysorbate 60, polysorbate 80, (partially peppermint oil, vanilla powder flavor 5428632, tetrasodium Saponified) polyvinyl alcohol, potassium polyphosphate, pyrophosphate, Wine, glucose, glucose-fructose Syrup, Sodium polyphosphate, macrogol 300, macrogol 400, mac fumaric acid, monosodium fumarate, peppermint powder, rogol 4000, maleic acid, malonic acid, magnesium alumi poVidone, maltitol, maltitol Solution, malt extract, maltose, nometasilicate, Sodium metaphosphate, methyl cellulose, millefolium herb dry extract, methyl cellulose, menthol methyl hesperidin, aluminum monoStearate, glycerol powder, eucalyptus oil, borneol, borneol powder, Ringer's monoStearate, eucalyptus oil, Sodium lauryl Sulfate, borneol Solution, apple juice, apple Vinegar, concentrated apple juice powder, malic acid, phosphoric acid, Sodium hydrogen (500%), lemon oil, rose water, rose oil, royal jelly, Syrup, phosphate, potassium dihydrogen phosphate, calcium dihy Sodium chloride, magnesium chloride, hydrochloric acid, drogen phosphate, Sodium Sulfite, Sodium hydrogen Sulfite, fructose, fructose-glucose Syrup, dry yeast, hydrogenated benzoic acid, Sodium benzoate, benzyl benzoate, calcium maltose Starch Syrup, diluted hydrochloric acid, high glucose chloride, Sodium chloride, magnesium chloride, hydrochlo Starch Syrup, high fructose Syrup, brown Sugar, tartaric acid, ric acid, arginine hydrochloride, cysteine hydrochloride, potassium hydrogen tartrate, edible carrot powder, acetic fructose, dry Sodium Sulfite, dry Sodium carbonate, hydrous acid, Starch Syrup, purified glycyrrhiza extract powder, puri Silicon dioxide, diluted hydrochloric acid, light Silicic anhy fied honey, purified Sucrose, purified Sucrose spherical gran dride, crystalline cellulose, hydrogenated oil, magnesium ules, Skim milk powder, Simple Syrup, Sodium hydrogen US 2004/O147605 A1 Jul. 29, 2004 carbonate, medium-chain triglyceride, Sodium copper chlo macodyn. Ther., vol. 304, p. 277, 1990), the guinea pigs rophyllin, lactic acid, lactose, concentrated glycerol, plum were exposed to SO gas using an exposure apparatus for extract, Sucrose, glacial acetic acid, powder Sugar, hydroge two hours a day in eight consecutive days to cause respira nated maltose powder Starch Syrup, anhydrous ethanol, citric tory tract inflammation. The Samples of which the compo anhydride, anhydrous Sodium pyrophosphate, ethyl lactate, nents and dose are shown in Table 1 were orally adminis and green tea powder. tered before exposure to SO gas once a day in eight consecutive days Since the Start date of exposure. The guinea 0050 Specific examples of the adsorbent include kaolin, pigs were confined in a chamber without being anesthetized. carmellose calcium, hydrous Silicon dioxide, magnesium On the date following the last SO exposure date, capsaicin Silicate, light Silicic anhydride, diatomite, crystalline cellu (10 mol/l) was sprayed over the chamber for two minutes lose, Synthetic aluminum Silicate, aluminum oxide, alumi using a ultrasonic nebulizer (TUR-3200, Nihon Kohden num hydroxide, magnesium carbonate, precipitated calcium Corporation) to cause cough in the guinea pigs. The reaction carbonate, dextrin, Silicon dioxide, bentonite, magnesium was observed for two minutes during spraying and 13 aluminometasilicate, and medicinal charcoal. minutes following the spraying (15 minutes in total). The 0051 Specific examples of the antifoaming agent include frequency of cough during this period was counted. ethanol, glycerol fatty acid ester, dimethylpolysiloxane (for internal use), dimethylpolysiloxane-Silicon dioxide mixture, 0061 (Results) Sucrose fatty acid ester, Silicon resin emulsion, Silicon anti foaming agent, polyoxyl 40 Stearate, Sorbitan fatty acid TABLE 1. ester, Sorbitan trioleate, and polySorbate 80. Test group Frequency of cough 0.052 Specific examples of the masticatory include Control group 22.4 - 0.8 d-borneol. Fudosteine 30 mg/kg 22.6 11 Dextromethorphan 150 mg/kg 13.6 1.0 ** 0.053 Specific examples of the colorant include gambir Dextromethorphan 300 mg/kg 10.2 + 0.6 **, tannin powder, turmelic extract Solution, yellow diron tri Fudosteine (30 mg/kg) + Dextromethorphan 7.2 : 0.7 ses, #, ss oxide, Opaspray K-1-24904, orange essence, brown iron (150 mg/kg) oxide, carbon black, caramel, carmine, caroteine Solution, Fudosteine (30 mg/kg) + Dextromethorphan B-caroteine, glycyrrhiza extract, gold foil, black iron oxide, (300 mg/kg) light Silicic anhydride, titanium oxide, diron trioxide, food **: p < 0.01, for control group ": p < 0.01, for fudosteine 30 mg/kg group blue 1, food yellow 4, food yellow 4 aluminum lake, food : p < 0.05, for dextromethorphan 150 mg/kg group yellow 5, food red 2, food red 3, food red 102, Sodium : p <0.01, for dextromethorphan 150 mg/kg group hydroxide, talc, Sodium copper chlorophyllin, copper chlo '': p <0.01, for dextromethorphan 300 mg/kg group rophyll, green barley leaf extract, d-borneol, octyldodecyl myristate, medicinal charcoal, riboflavin butyrate, ribofla Vin, green tea powder, and riboflavin Sodium phosphate, and 0062) These results show that fudosteine did not exhibit rose oil. an antituSSive effect when administered alone. In contrast, dextromethorphan exhibited an antitussive effect when 0.054 Specific examples of the soothing agent include administered alone. Its antituSSive effect was enhanced by inositol, Sodium hydrogen carbonate, clove oil, glucose, administration in combination with fudosteine. The dose propylene glycol, and lidocaine. response was also observed. The Synergetic effect on the 0055. In the drug preparation of the present invention antituSSive effects of using the two medicinal components in obtained as above, fudosteine acts on an antituSSive to combination was exhibited. AS is clear from these results, enhance that effect. Therefore, the preparation is markedly the antitussive effect of the antitussive was enhanced by useful as a drug preparation with an excellent antituSSive using fudosteine in combination. effect, particularly as a drug preparation for colds or an antituSSive expectorant. Example 1 EXAMPLES 0063 Tablet Preparation: 0064.) Fudosteine (1,200 g), dextromethorphan hydrobro 0056. The present invention will be described in more mide (60 g), corn Starch (38 g), talc (1 g), and magnesium detail with reference to Examples and Test Examples which Stearate (1 g) were made into a powder for tableting by a should not be construed as limiting the present invention. conventional method. The powder was tableted using a Test Example 1 rotary tableting machine to prepare a tablet preparation in which each tablet had a diameter of 8.5 mm and a weight of 0057 Antitussive Effect Test: 250 mg. 0.058. The synergetic effect of using fudosteine and an antituSSive compound in combination was examined accord Example 2 ing to the following method. The results are shown in Table 0065 Liquid Preparation: 1. 0066 Fudosteine (8 g), dextromethorphan hydrobromide 0059) (Method) (400 mg), erythritol (20 g), caramel (100 mg), sodium 0060 Five male Hartley guinea pigs for one group, each benzoate (70 mg), and flavor (100 mg) were dissolved in having a weight of 300-400 g, were used as test animals. purified water. An appropriate amount of phosphoric acid According to the method of Miyata et al. (Arch. Int. Phar was added to the mixture to adjust the pH, followed by US 2004/O147605 A1 Jul. 29, 2004 adding purified water to the mixture to make the total Example 5 amount 100 ml, to prepare a liquid preparation. 0071 Liquid Preparation: 0072 Fudosteine (12.8 g), codein phosphate (0.2 g), Example 3 d1-methylephedrine hydrochloride (0.3 g), lyZozyme hydro chloride (0.24 g, titer), chlorpheniramine maleate (48 mg), 0067 Tablet Preparation: anhydrous caffeine (0.24g), Senega powder extract (60 g), erythritol (60g), and flavor (0.4 g) were dissolved in purified 0068 Fudosteine (120 g), dihydrocodeine phosphate (3 water. An appropriate amount of phosphoric acid was added g), dl-methylephedrine hydrochloride (5 g), chlorphe to the mixture to adjust the pH, followed by adding purified niramine maleate (0.8 g), anhydrous caffeine (9 g), potato water to the mixture to make the total amount 240 ml, to Starch (159.8 g), talc (1.2 g), and magnesium Stearate (1.2 g) prepare a liquid preparation. were made into a powder for tableting by a conventional method. The powder was tableted using a rotary tableting 1. A drug preparation comprising fudosteine and a medi cine possessing an antituSSive effect. machine to prepare a tablet preparation in which each tablet 2. The drug preparation according to claim 1, wherein the had a diameter of 8.5 mm and a weight of 250 mg. preparation is a preparation to be orally administered. 3. The drug preparation according to claim 1 or 2, wherein Example 4 the preparation is an antituSSive expectorant. 4. The drug preparation according to any one of claims 0069 Granule Preparation: 1-3, further comprising one or more medicines Selected from 0070 Fudosteine (120 g), dihydrocodeine phosphate (3 the group consisting of a bronchodilator, antihistamine, g), lyZozyme hydrochloride (3.3 g), chlorpheniramine male analeptic, galenical, bactericide, and antacid or mucosal ate (7.5 g), corn starch (89.7g), and trehalose (83.25 g) were protective agent. made into a granule preparation by a conventional method.